Metabolites are the intermediate products of metabolic reactions catalyzed by various enzymes that naturally occur within cells. The term metabolite is usually used for small molecules.
Metabolites forms may be integral or pharmacological and formed during the natural biochemical process of degrading and eliminating the compounds from chemical compounds. It is important to know how the drug products are metabolized and what are its probable side effects. e.g. Sugars are metabolites into fructose or glucose, which are both present in the metabolic pathways.
Regulatory Guidance documents ICH Q3A (R2) and ICH Q3B (R2) state that “impurities that are also significant metabolites present in animal and/or human studies are generally considered qualified”. But no guidance is provided regarding data requirements for qualification.
Metabolite impurities are by-products and formed in the body after ingesting of drug products.
Some metabolites are formed as impurities during the drug substance or drug product development process or storage. Control of these process-related metabolite impurities in the final drug substance may not be necessary if control of other metabolites has already occurred and taken into consideration.
Detection limits of the drugs and their metabolites is very much important. HPLC, HPLC-MS/MS is the main analytical method for regular analysis as well as pharmacokinetic and metabolism studies due to its inherent specificity, sensitivity, and speed.
Metabolite quantification is essential when the metabolite is toxic or pharmacologically active or when the concentration of metabolite reaches or exceeds the parent drug concentration in plasma. Following are the list of sophisticated analytical instruments used for the identification and quantification
HPLC with UV, Fluorescence or Electrochemical Detection, HPLC-MS/MS, MS with high-resolution detector Triple TOF and QTrap, Nuclear magnetic resonance (NMR) spectroscopy, Capillary electrophoresis (CE), GC-MS, etc.
Metabolic changes of drugs can be responsible for problems associated with their bioavailability, interindividual variability, drug-drug interactions, pharmacologic activity or the toxicity. An effective analytical method for identification, quantification, and monitoring of drug metabolism is to be developed and validated. HPLC with MS is a very much important analytical technique for the identification and quantification of drug metabolites.